Pre-synaptic and post-synaptic development in the central nervous system will be studied using cultures of mouse brain. The objectives of this project are to define: 1) any interrelations between pre- and post-synaptic elements; and 2) any effects of drugs of abuse on these elements. Pre-synaptic development will be studied following the development of 1) enzymes that synthesize acetylcholine, gamma-amino butyric acid and catecholamines and 2) systems that transport monoamine neurotransmitters. Post-synaptic development will be studied by determining the development of receptors for acetylcholine (muscarinic), gamma-amino butyric acid, glycine, serotonin, and opiates as measured by binding of radioactively labelled quinuclidinyl benzilate (QNB), gamma-amino butyric acid, strychnine, d-LSD and naloxone, respectively. By studying this development when cells are chronically grown in the presence of certain drugs of abuse, the effects of these agents on pre-and post-synaptic development will be determined. BIBLIOGRAPHIC REFERENCES: Honegger, P. and Richelson, E. (1977). Biochemical differentiation of aggregating cell cultures of different fetal rat brain regions, Brain Research, in press. Honegger, P. and Richelson, E. (1977). Neurotransmitter synthesis by aggregating cultures of rat CNS, Transactions of the American Society for Neurochemistry, Vol. 8, No, 1, in press.